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130
Cellular Respiration: Harvesting Chemical Energy
Formation of Acetyl CoA. The junction between glycolysis and the Krebs Cycle is the oxidation
of pyruvate to acetyl CoA:
• Pyruvate molecules are translocated from
the cytosol into the mitochondrion by a
carrier protein in the mitochondrial
membrane.
Coenzyme A
3
OH
C
CO2
S
CoA
C
O
1
O
}
2
Acetyl
C O
• This step is catalyzed by a multienzyme
group
CH
3
NAD+
NADH
complex which:
CH3
+H+
Acetyl
1. Removes CO2 from the carboxyl group
Pyruvate
Coenzyme
A
of pyruvate, changing it from a threecarbon to a two-carbon compound.
This is the first step where CO2 is released.
2. Oxidizes the two-carbon fragment to acetate, while reducing NAD+ to NADH. Since
glycolysis produces two pyruvate molecules per glucose, there are two NADH molecules
produced.
3. Attaches coenzyme A to the acetyl group, forming acetyl CoA. This bond is unstable,
making the acetyl group very reactive.
Krebs Cycle: The Krebs Cycle reactions oxidize the remaining acetyl fragments of acetyl-CoA to
CO2. Energy released from this exergonic process is used to reduce coenzyme (NAD+ and FAD)
and to phosphorylate ATP (substrate-level phosphorylation).
• A German-British scientist, Hans Krebs, elucidated this catabolic pathway in the 1930's.
• The Krebs cycle, which is also known as the citric acid cycle or TCA cycle, has eight
enzyme-controlled steps that occur in the mitochondrial matrix.
For every turn of Krebs Cycle:
Acetyl CoA
• Two carbons enter in the acetyl
fragment of acetyl CoA.
2 carbons enter cycle
• Two different carbons are oxidized
and leave as CO2.
NADH
• Coenzymes are reduced; three
NADH and one FADH2 are
produced.
NAD
• One ATP molecule is produced by
substrate-level phosphorylation.
• Oxaloacetate is regenerated.
Oxaloacetate
+
Citrate
Krebs Cycle
CO2 leaves cycle
Malate
(Substrate
phosphorylation)
ATP
FADH2
FAD
NAD
ADP
+
Pi
+
NADH
α–Ketoglutarate
Succinate
CO2 leaves cycle
Carbons
+
NADH
NAD
131
Cellular Respiration: Harvesting Chemical Energy
For every glucose molecule split during glycolysis:
• Two acetyl fragments are produced.
• It takes two turns of Krebs Cycle to complete the oxidation of glucose.
Steps of the Krebs Cycle: (This detailed description is now in the appendix of the Campbell
text.)
Step 1: The unstable bond of acetyl CoA
breaks, and the two-carbon acetyl group
bonds to the four-carbon oxaloacetate to form
six-carbon citrate.
S
CoA
C
O
COO
CH 3
CH 2
Acetyl CoA
HO
C
COO
C
COO
CH 2
COO
CoA–SH
O
Citrate
CH 2
COO
Oxaloacetate
Step 2: Citrate is isomerized to isocitrate.
H2O
COO
COO
CH2
C
HO
CH 2
COO
HC
HO
CH2
Step 3: Two major events occur during this
step:
• Isocitrate loses CO2 leaving a fivecarbon molecule.
• The five-carbon compound
oxidized and NAD+ is reduced.
is
Step 4: A multienzyme complex catalyzes:
• Removal of CO2.
• Oxidation of the remaining four-carbon
compound and reduction of NAD+.
• Attachment of CoA with a high energy
bond to form succinyl CoA.
COO
Citrate
Isocitrate
COO
CO2
CH 2
HO
CH
COO
COO
HC
COO
CH 2
COO
CH 2
CH
O
C
+
NAD
COO
COO
NADH
Isocitrate
α–Ketogluterate
+
+H
COO
CO2
CoA–SH
CH2
CH2
CH 2
C
COO
CH2
O
COO
NAD
α–Ketoglutarate
+
NADH
+
+H
C
O
S
CoA
Succinyl CoA
132
Cellular Respiration: Harvesting Chemical Energy
Step 5: Substrate-level phosphorylation occurs
in a series of enzyme catalyzed reactions:
COO
• The high energy bond of succinyl-CoA
breaks, and some energy is conserved as
CoA is displaced by a phosphate group.
• The phosphate group is transferred to
GDP to form GTP and succinate.
COO
CoA–SH
CH 2
CH 2
CH 2
C
O
S
CoA
CH 2
GDP
+ Pi
Succinate
Succinyl CoA
• GTP donates a phosphate group to ADP
to form ATP.
ADP
ATP
Step 6: Succinate is oxidized to fumarate and
FAD is reduced.
• Two hydrogens are transferred to FAD
to form FADH2.
COO
COO
CH 2
CH
CH 2
HC
COO
• The dehydrogenase that catalyzes this
reaction is bound to the inner
mitochondrial membrane.
COO
GTP
FAD
FADH2
Succinate
Step 7: Water is added to fumarate which rearranges
its chemical bonds to form malate.
COO
Fumarate
COO
COO
HO
CH
CH
CH 2
H– C
COO
H2O
COO
Malate
Fumarate
Step 8: Malate is oxidized and NAD+ is
reduced.
• A molecule of NADH is produced.
• Oxaloacetate is regenerated to begin the
cycle again.
HO
COO
COO
CH
C
CH 2
COO
O
CH 2
NAD
+
Malate
NADH
+H
+
COO
Oxaloacetate
Two turns of the Krebs Cycle produces two ATPs by substrate-level phosphorylation. However,
most ATP output of respiration results from oxidative phosphorylation.
• Reduced coenzymes produced by the Krebs Cycle (6 NADH and 2 FADH2 per glucose)
carry high energy electrons to the electron transport chain.
• The ETC couples electron flow down the chain to ATP synthesis.
Cellular Respiration: Harvesting Chemical Energy
IX.
133
The inner mitochondrial membrane couples electron transport to ATP synthesis: a closer
look
Only a few molecules of ATP are produced by substrate-level phosphorylation:
• 2 net ATPs per glucose from glycolysis.
• 2 ATPs per glucose from the Krebs Cycle.
Most molecules of ATP are produced by oxidative phosphorylation.
• At the end of the Krebs Cycle, most of the energy extracted from glucose is in molecules of
NADH and FADH2.
• These reduced coenzymes link glycolysis and the Krebs Cycle to oxidative phosphorylation
by passing their electrons down the electron transport chain to oxygen. (Though the Krebs
Cycle occurs only under aerobic conditions, it does not use oxygen directly. The ETC and
oxidative phosphorylation require oxygen as the final electron acceptor.)
• This exergonic transfer of electrons down the ETC to oxygen is coupled to ATP synthesis.
A.
The Pathway of Electron Transport
The electron transport chain is made of electron carrier molecules embedded in the inner
mitochondrial membrane.
• Each successive carrier in the chain has a higher electronegativity than the carrier
before it, so the electrons are pulled downhill towards oxygen, the final electron
acceptor and the molecule with the highest electronegativity.
• Except for ubiquinone (Q), most of the carrier molecules are proteins and are tightly
bound to prosthetic groups (nonprotein cofactors).
• Prosthetic groups alternate between reduced and oxidized states as they accept and
donate electrons.
Protein Electron Carriers
flavoproteins
iron-sulfur proteins
cytochromes
Prosthetic Group
flavin mononucleotide (FMN)
iron and sulfur
heme group
Heme group = Prosthetic group composed of four organic rings surrounding a single iron
atom.
Cytochrome = Type of protein molecule that contains a heme prosthetic group and that
functions as an electron carrier in the electron transport chains of mitochondria and
chloroplasts.
• There are several cytochromes, each a slightly different protein with a heme group.
• It is the iron of cytochromes that transfers electrons.
134
Cellular Respiration: Harvesting Chemical Energy
Sequence of Electron Transfers Along the Electron Transport Chain:
NADH is oxidized and flavoprotein is
reduced as high energy electrons from
NADH are transferred to FMN.
NADH
50
Flavoprotein is oxidized as it passes
electrons to an iron-sulfur protein, Fe•S.
FADH2
40
FMN
Iron-sulfur protein is oxidized as it passes
electrons to ubiquinone (Q).
Q
Cyt b
30
Ubiquinone passes electrons on to a
succession of electron carriers, most of
which are cytochromes.
Cyt a3, the last cytochrome passes
electrons to molecular oxygen, O2.
As molecular oxygen is reduced it also
picks up two protons from the medium to
form water. For every two NADHs, one
O2 is reduced to two H2O molecules.
Fe•S
Fe•S
Fe•S
Cyt c1
Cyt c
Cyt a
Cyt a3
20
10
0
½
O2
• FADH2 also donates electrons to the electron transport chain, but those electrons are
added at a lower energy level than NADH.
• The electron transport chain does not make ATP directly. It generates a proton
gradient across the inner mitochondrial membrane, which stores potential energy that
can be used to phosphorylate ADP.
B.
Chemiosmosis: The Energy-Coupling Mechanism
The mechanism for coupling exergonic electron flow from the oxidation of food to the
endergonic process of oxidative phosphorylation is chemiosmosis.
Chemiosmosis = The coupling of exergonic electron flow down an electron transport chain to
endergonic ATP production by the creation of a proton gradient across a membrane. The
proton gradient drives ATP synthesis as protons diffuse back across the membrane.
• Proposed by British biochemist, Peter Mitchell (1961).
• The term chemiosmosis emphasizes a coupling between (1) chemical reactions
(phosphorylation) and (2) transport processes (proton transport).
Cellular Respiration: Harvesting Chemical Energy
135
• Process involved in oxidative phosphorylation and photophosphorylation.
The site of oxidative phosphorylation is the
Inner membrane
Outer membrane
inner mitochondrial membrane, which has
Cristae
many copies of a protein complex, ATP
synthase. This complex:
• Is an enzyme that makes ATP.
• Uses an existing proton gradient across
the inner mitochondrial membrane to
Intermembrane space
power ATP synthesis.
high H+ concentration
Matrix
low H+ concentration
Cristae or infoldings of the inner mitochondrial membrane, increase the surface area
available for chemiosmosis to occur.
Membrane structure correlates with the prominent functional role membranes play in
chemiosmosis:
• Using energy from exergonic
electron flow, the electron
transport chain creates the proton
gradient by pumping H+s from the
mitochondrial matrix, across the
inner membrane to the intermembrane space.
• This proton gradient is maintained,
because
the
membrane's
phospholipid
bilayer
is
impermeable to H+s and prevents
them from leaking back across the
membrane by diffusion.
Intermembrane
space
H+
+ + + + + + + + + + + + + + + + + + + + + +
Electron
transport
chain
- - - - - - - - - - - - - - - - - - - - - - - - - - ATP
synthase
Matrix
ADP
• ATP synthases use the potential
ATP
+
energy stored in a proton gradient
Pi
to make ATP by allowing H+ to
diffuse down the gradient, back
across the membrane. Protons diffuse through the ATP synthase complex, which
causes the phosphorylation of ADP.
How does the electron transport chain pump hydrogen ions from the matrix to the
intermembrane space? The process is based on spatial organization of the electron
transport chain in the membrane. Note that:
• Some electron carriers of the transport chain transport only electrons.
• Some electron carriers accept and release protons along with electrons. These carriers
are spatially arranged so that protons are picked up from the matrix and are released
into the intermembrane space.
136
Cellular Respiration: Harvesting Chemical Energy
Most of the electron carriers are organized into three complexes: 1) NADH dehydrogenase
complex; 2) cytochrome b-c1 complex; and 3) cytochrome oxidase complex. (See Campbell,
Figure 9.14)
• Each complex is an asymmetric particle that has a specific orientation in the
membrane.
• As complexes transport electrons, they also harness energy from this exergonic
process to pump protons across the inner mitochondrial membrane.
Mobile carriers transfer electrons between complexes. These mobile carriers are:
1. Ubiquinone (Q).
Near the matrix, Q accepts electrons from the NADH
dehydrogenase complex, diffuses across the lipid bilayer, and passes electrons to the
cytochrome b-c1 complex.
2. Cytochrome c (Cyt c). Cyt c accepts electrons from the cytochrome b-c1 complex
and conveys them to the cytochrome oxidase complex.
When the transport chain is operating:
• The pH in the intermembrane space is one or two pH units lower than in the matrix.
• The pH in the intermembrane space is the same as the pH of the cytosol because the
outer mitochondrial membrane is permeable to protons.
The H+ gradient that results is called a proton-motive force to emphasize that the gradient
represents potential energy.
Proton motive force = Potential energy stored in the proton gradient created across biological
membranes that are involved in chemiosmosis.
• This force is an electrochemical gradient with two components:
1. Concentration gradient of protons (chemical gradient).
2. Voltage across the membrane because of a higher concentration of positively
charged protons on one side (electrical gradient).
• It tends to drive protons across the membrane back into the matrix.
Chemiosmosis couples exergonic chemical reactions to endergonic H+ transport, which
creates the proton-motive force used to drive cellular work, such as:
• ATP synthesis in mitochondria (oxidative phosphorylation). The energy to create the
proton gradient comes from the oxidation of glucose and the ETC.
• ATP synthesis in chloroplasts (photophosphorylation). The energy to create the
proton gradient comes from light trapped during the energy-capturing reactions of
photosynthesis.
• ATP synthesis, transport processes and rotation of flagella in bacteria. The proton
gradient is created across the plasma membrane. Peter Mitchell first postulated
chemiosmosis as an energy-coupling mechanism based on experiments with bacteria.
Cellular Respiration: Harvesting Chemical Energy
C.
137
Biological Themes and Oxidative Phosphorylation
The working model of how mitochondria harvest the energy of food, illustrates many of the
text's integrative themes in the study of life:
• Energy conversion and utilization.
• Emergent properties. Oxidative phosphorylation is an emergent property of the intact
mitochondrion that uses a precise interaction of molecules.
• Correlation of structure and function. The chemiosmotic model is based upon the
spatial arrangement of membrane proteins.
• Evolution. In an effort to reconstruct the origin of oxidative phosphorylation and the
evolution of cells, biologists compare similarities in the chemiosmotic machinery of
mitochondria to that of chloroplasts and bacteria.
X.
Cellular respiration generates many ATP molecules for each sugar molecule it
oxidizes: a review
During cellular respiration, most energy flows in this sequence:
Glucose ⇒ NADH ⇒ electron transport chain ⇒ proton motive force ⇒ ATP
The net ATP yield from the oxidation of one glucose molecule to six carbon dioxide molecules can
be estimated by adding:
1. ATP produced directly by substrate-level phosphorylation during glycoloysis and the Krebs
cycle.
• A net of two ATPs is produced during glycolysis. The debit of two ATPs used during
the investment phase is subtracted from the four ATPs produced during the energyyielding phase.
• Two ATPs are produced during the Krebs cycle.
2. ATP produced when chemiosmosis couples electron transport to oxidative phosphorylation.
• The electron transport chain creates enough proton-motive force to produce a maximum
of three ATPs for each electron pair that travels from NADH to oxygen. The average
yield is actually between two and three ATPs per NADH (2.7).
• FADH2 produced during the Krebs Cycle is worth a maximum of only two ATPs, since
it donates electrons at a lower energy level to the electron transport chain.
• In most eukaryotic cells, the ATP yield is lower from an NADH produced during
glycolysis. The mitochondrial membrane is impermeable to NADH, so its electrons
must be carried across the membrane in another molecule. These electrons are received
inside the mitochondrion by FAD, a process which downgrades the energy level of those
electrons.
138
Cellular Respiration: Harvesting Chemical Energy
• Maximum ATP yield for each glucose oxidized during cellular respiration:
ATP Produced
Directly by
Substrate-Level
Phosphorylation
Reduced
Coenzyme
ATP Produced
by Oxidative
Phosphorylation
Total
Net 2 ATP
2 NADH
4 to 6 ATP
6-8
Oxidation of
Pyruvate
_____
2 NADH
6 ATP
6
Krebs
Cycle
2 ATP
6 NADH
2 FADH2
18 ATP
4 ATP
24
Process
Glycolysis
Total
36-38
• This tally only estimates the ATP yield from respiration. Some variables that affect
ATP yield include:
⇒ The proton-motive force may be used to drive other kinds of cellular work such as
active transport.
⇒ The total ATP yield is inflated (∼10%) by rounding off the number of ATPs
produced per NADH to three.
Cellular respiration is remarkably efficient in the transfer of chemical energy from glucose to ATP.
• Estimated efficiency in eukaryotic cells is about 38%.
• Energy lost in the process is released as heat.
XI.
Fermentation enables some cells to produce ATP without the help of oxygen
Food can be oxidized under anaerobic conditions.
Aerobic = (Aer = air; bios = life) Existing in the presence of oxygen.
Anaerobic = (An = without; aer = air) Existing in the absence of free oxygen.
Fermentation = The anaerobic catabolism of organic nutrients.
Glycolysis oxidizes glucose to two pyruvate molecules, and the oxidizing agent for this process is
NAD+, not oxygen.
• Some energy released from the exergonic process of glycolysis drives the production of 2 net
ATPs by substrate-level phosphorylation.
• Glycolysis produces a net of 2 ATPs whether conditions are aerobic or anaerobic.
1. Aerobic conditions: Pyruvate is oxidized further, and more ATP is made as NADH
passes electrons removed from glucose to the electron transport chain. NAD+ is
regenerated in the process.
Cellular Respiration: Harvesting Chemical Energy
139
2. Anaerobic conditions: Pyruvate is reduced, and NAD+ is regenerated. This prevents
the cell from depleting the pool of NAD+, which is the oxidizing agent necessary for
glycolysis to continue. No additional ATP is produced.
Fermentation recycles NAD+ from NADH. This process consists of anaerobic glycolysis plus
subsequent reactions that regenerate NAD+ by reducing pyruvate. Two of the most common types
of fermentation are (1) alcohol fermentation and (2) lactic acid fermentation. (See Campbell,
Figure 9.16)
1. Alcohol Fermentation
2 ADP
+
2 Pi
Glucose
2 NAD
+
2 NADH
+2H
+
2 NADH
–
O
|
C= O
|
C= O
|
CH3
2 ATP
2 CO2
+2H
H
|
C=O
|
CH3
2 NAD
H
|
H–C–OH
|
CH3
2 Ethanol
2 Acetaldehyde
2 Pyruvate
+
+
Pyruvate is converted to ethanol in two steps:
a. Pyruvate loses carbon dioxide and is converted to the two-carbon compound
acetaldehyde.
b. NADH is oxidized to NAD+ and acetaldehyde is reduced to ethanol.
Many bacteria and yeast carry out alcohol fermentation under anaerobic conditions.
2. Lactic Acid Fermentation
2 ADP
+
2 Pi
–
2 ATP
Glucose
2 NAD
+
2 NADH
+
+2H
O
|
C=O
|
C=O
|
CH3
2 Pyruvate
2 NADH
+2H
+
–
2 NAD
+
O
|
C=O
|
H–C–OH
|
CH3
2 Lactate
15
+
NADH is oxidized to NAD and pyruvate is reduced to lactate.
• Commercially important products of lactic acid fermentation include cheese and
yogurt.
• When oxygen is scarce, human muscle cells switch from aerobic respiration to lactic
acid fermentation. Lactate accumulates, but it is gradually carried to the liver where
it is converted back to pyruvate when oxygen becomes available.
140
Cellular Respiration: Harvesting Chemical Energy
A.
Comparison of Fermentation and Respiration
The anaerobic process of fermentation and aerobic process of cellular respiration are similar
in that both metabolic pathways:
• use glycolysis to oxidize glucose and other substrates to pyruvate, producing a net of 2
ATPs by substrate phosphorylation.
• use NAD+ as the oxidizing agent that accepts electrons from food during glycolysis.
Fermentation and cellular respiration differ in:
• how NADH is oxidized back to NAD+. Recall that the oxidized form, NAD+, is
necessary for glycolysis to continue.
⇒ During fermentation, NADH passes electrons to pyruvate or some derivative. As
pyruvate is reduced, NADH is oxidized to NAD+. Electrons transferred from
NADH to pyruvate or other substrates are not used to power ATP production.
⇒ During cellular respiration, the stepwise electron transport from NADH to oxygen
not only drives oxidative phosphorylation, but regenerates NAD+ in the process.
• the final electron acceptor.
⇒ In fermentation, the final electron acceptor is pyruvate (lactic acid fermentation),
acetaldehyde (alcohol fermentation), or some other organic molecule.
⇒ In cellular respiration, the final electron acceptor is oxygen.
• the amount of energy harvested.
⇒ During fermentation, energy stored in pyruvate is unavailable to the cell.
⇒ Cellular respiration yields 18 times more ATP per glucose molecule than does
fermentation. The higher energy yield is a consequence of the Krebs Cycle which
completes the oxidation of glucose and thus taps the chemical bond energy still
stored in pyruvate at the end of glycolysis.
• their requirement for oxygen.
⇒ Fermentation does not require oxygen.
⇒ Cellular respiration occurs only in the presence of oxygen.
Organisms can be classified based upon the effect oxygen has on growth and metabolism.
Strict (obligate) aerobes = Organisms that require oxygen for growth and as the final
electron acceptor for aerobic respiration.
Strict (obligate) anaerobes = Microorganisms that only grow in the absence of oxygen and
are, in fact, poisoned by it.
Cellular Respiration: Harvesting Chemical Energy
141
Facultative anaerobes = Organisms capable of growth in either aerobic or anaerobic
environments.
• Yeasts, many bacteria and mammalian muscle cells are facultative anaerobes.
• Can make ATP by fermentation in the absence of oxygen or by respiration in the
presence of oxygen.
• Glycolysis is common to both fermentation and respiration, so pyruvate is a key
juncture in catabolism.
glucose
glycolysis
no O2
O2
pyruvate
reduced to ethanol
or lactate
&
NAD+ is recycled
as NADH is oxidized.
B.
oxidized to
acetyl CoA
&
oxidation continues
in Krebs cycle.
The Evolutionary Significance of Glycolsysis
The first prokaryotes probably produced ATP by glycolysis.
following:
Evidence includes the
• Glycolysis does not require oxygen, and the oldest known bacterial fossils date back to
three-and-a-half billion years ago when oxygen was not present in the atmosphere.
• Glycolysis is the most widespread metabolic pathway, so it probably evolved early.
• Glycolysis occurs in the cytosol and does not require membrane-bound organelles.
Eukaryotic cells with organelles probably evolved about two billion years after
prokaryotic cells.
XII.
Glycolysis and the Krebs cycle connect to many other metabolic pathways
A.
The Versatility of Catabolism
Respiration can oxidize organic molecules other than glucose to make ATP. Organisms
obtain most calories from fats, proteins, disaccharides and polysaccharides. These complex
molecules must be enzymatically hydrolyzed into simpler molecules or monomers that can
enter an intermediate reaction of glycolysis or the Krebs cycle. (See Campbell, Figure 9.19)
142
Cellular Respiration: Harvesting Chemical Energy
Glycolysis can accept a wide range of carbohydrates for catabolism.
• Starch is hydrolyzed to glucose in the digestive tract of animals.
• In between meals, the liver hydrolyzes glycogen to glucose.
• Enzymes in the small intestine break down disaccharides to glucose or other
monosaccharides.
Proteins are hydrolyzed to amino acids.
• Organisms synthesize new proteins from some of these amino acids.
• Excess amino acids are enzymatically converted to intermediates of glycolysis and the
Krebs cycle. Common intermediates are pyruvate, acetyl CoA and α-ketoglutarate.
• This conversion process deaminates amino acids, and the resulting nitrogenous wastes
are excreted.
Fats are excellent fuels because they are rich in hydrogens with high energy electrons.
Oxidation of one gram of fat produces twice as much ATP as a gram of carbohydrate.
• Fat sources may be from the diet or from storage cells in the body.
• Fats are digested into glycerol and fatty acids.
• Glycerol can be converted to glyceraldehyde phosphate, an intermediate of glycolysis.
• Most energy in fats is in fatty acids, which are converted into acetyl CoA by beta
oxidation. The resulting two-carbon fragments can enter the Krebs cycle.
B.
Biosynthesis (Anabolic Pathways)
Some organic molecules of food provide the carbon skeletons or raw materials for the
synthesis of new macromolecules.
• Some organic monomers from digestion can be used directly in anabolic pathways.
• Some precursors for biosynthesis do not come directly from digested food, but instead
come from glycolysis or Krebs cycle intermediates which are diverted into anabolic
pathways.
• These anabolic pathways consume ATP produced by catabolic pathways of glycolysis
and respiration.
• Glycolysis and the Krebs cycle are metabolic interchanges that can convert one type of
macromolecule to another in response to the cell's metabolic demands.
Cellular Respiration: Harvesting Chemical Energy
143
XIII. Feedback mechanisms control cellular respiration
Cells respond to changing metabolic needs by controlling reaction rates.
• Anabolic pathways are switched off when their products are in ample supply. The most
common mechanism of control is feedback inhibition. (See Campbell, Chapter 6.)
• Catabolic pathways, such as glycolysis and Krebs cycle, are controlled by regulating enzyme
activity at strategic points.
A key control point of catabolism is the third step of glycolysis, which is catalyzed by an allosteric
enzyme, phosphofructokinase.
• The ratio of ATP to ADP and AMP reflects the energy status of the cell, and
phosphofructokinase is sensitive to changes in this ratio.
• Citrate (produced in Krebs cycle) and ATP are allosteric inhibitors of phosphofructokinase,
so when their concentrations rise, the enzyme slows glycolysis. As the rate of glycolysis
slows, Krebs cycle also slows since the supply of acetyl CoA is reduced. This synchronizes
the rates of glycolysis and Krebs cycle.
• ADP and AMP are allosteric activators for phosphofructokinase, so when their
concentrations relative to ATP rise, the enzyme speeds up glycolysis which speeds up the
Krebs cycle.
• There are other allosteric enzymes that also control the rates of glycolysis and the Krebs
cycle.
REFERENCES
Campbell, N. Biology. 4th ed. Menlo Park, California: Benjamin/Cummings, 1996.
Lehninger, A.L., D.L. Nelson and M.M. Cox. Principles of Biochemistry. 2nd ed. New York: Worth,
1993.
Matthews, C.K. and K.E. van Holde. Biochemistry. 2nd ed. Redwood City, California:
Benjamin/Cummings, 1996.